Page 484 - IJB-10-2

International

Journal of Bioprinting

RESEARCH ARTICLE
Bioprinted autologous human skin equivalents

for in vitro testing of therapeutic antibodies

Mahid Ahmed , David Hill , Shaheda Ahmed , Stefan Przyborski , Kenneth
3,4
1,2
5,6
2
Dalgarno *, and Anne Dickinson 2,4
1
1 School of Engineering, Newcastle University, Newcastle upon Tyne, NE3 1PS, United Kingdom
2 Alcyomics Ltd., The Biosphere, Draymans Way, Newcastle Helix, Newcastle upon Tyne, NE4 5BX,
United Kingdom
3 Faculty of Health Sciences and Wellbeing, Sunderland University, Sunderland, SR1 3SD, United
Kingdom
4 Translational & Clinical Research Institute, Faculty of Medical Science, Medical School, Newcastle
University, Newcastle upon Tyne, NE2 4HH, United Kingdom
5 Department of Bioscience, Durham University, South Road, Durham, DH1 3LE, United Kingdom
6 Reprocell Europe Ltd., NETPark Plexus, Thomas Wright Way, Sedgefield, Co. Durham, TS21 3FD,
United Kingdom

Abstract

In recent years, advances in tissue engineering have brought forward the accessibility
of human skin equivalents for in vitro applications; however, the availability of human-
based engineered tissue models suitable for high-throughput screening of biologics
remains limited. Here, we report a method of manufacturing fully autologous (with
both fibroblasts and keratinocytes from the same donor) human skin equivalents
*Corresponding author:
Kenneth Dalgarno for determining preclinical therapeutic antibody adverse immune reactions in vitro.
(kenny.dalgarno@newcastle.ac.uk) Using a combination of precise solenoid microvalve-based bioprinting and 96-well
Citation: Ahmed M, Hill D, scale Alvetex inserts, autologous skin cells were bioprinted and cultured to develop
Ahmed S, Przyborski S, Dalgarno K, a scalable approach to manufacturing skin equivalents. We demonstrated that
Dickinson A. Bioprinted autologous fibroblasts and keratinocytes can be bioprinted with a high degree of precision while
human skin equivalents for in vitro
testing of therapeutic antibodies. maintaining viability post printing. Histological staining showed that the bioprinted
Int J Bioprint. 2024;10(2):1851. 96-well based skin equivalents were comparable to human skin. The fully autologous
doi: 10.36922/ijb.1851 human skin equivalents were co-cultured in vitro with autologous peripheral blood
Received: September 17, 2023 monocytes with and without muromonab-CD3 (OKT3) and natalizumab (Tysabri),
Accepted: January 10, 2024 biologics which are known to cause and inhibit adverse immune reactions (type
Published Online: March 11, 2024
IV hypersensitivity), respectively. Analysis of supernatants from skin-equivalent
Copyright: © 2024 Author(s). monocyte co-cultures revealed significant proinflammatory cytokine responses
This is an Open Access article (such as interferon gamma) in co-cultures treated with OKT3 when compared to
distributed under the terms of the
Creative Commons Attribution Tysabri and negative controls. Consequently, this study provides proof of concept
License, permitting distribution, that through a combination of bioprinting and Alvetex scaffold-based culture
and reproduction in any medium, systems, scalable human skin equivalents can be manufactured for high-throughput
provided the original work is
properly cited. identification of adverse immune reactions during preclinical stages of the drug
development process.
Publisher’s Note: AccScience
Publishing remains neutral with
regard to jurisdictional claims in
published maps and institutional Keywords: Autologous tissue models; Skin-equivalent models;
affiliations. Microvalve bioprinting; Transwell culture

Volume 10 Issue 2 (2024) 476 doi: 10.36922/ijb.1851